Trimethylsilyl iodide → HCID 57947401, compound

HRID 409878Notes

Reaction equation

HRID 409878 reaction equation
[C:1]1([C:7]2[CH:11]=[C:10]([NH:12][C:13](=[O:44])[O:14][CH2:15][C@@H:16]([N:30]([CH3:43])[C:31]([NH:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=3[Cl:42])=[O:32])[CH2:17][C@@H:18]([OH:29])[CH2:19][O:20][P:21]([O:26]CC)([O:23]CC)=[O:22])[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Si](I)(C)(C)C>C(#N)C>[C:1]1([C:7]2[CH:11]=[C:10]([NH:12][C:13](=[O:44])[O:14][CH2:15][C@@H:16]([N:30]([CH3:43])[C:31]([NH:33][CH2:34][C:35]3[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[C:36]=3[Cl:42])=[O:32])[CH2:17][C@@H:18]([OH:29])[CH2:19][O:20][P:21]([OH:26])([OH:23])=[O:22])[O:9][N:8]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

4

Reactant 2

HCID 85247Trimethylsilyl iodideHCID 57947816HCID 57947816, compound

Product 1

HCID 57947401HCID 57947401, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-5-(diethoxyphosphoryloxy)-4-hydroxypentyl 3-phenylisoxazol-5-ylcarbamate (56 mg, 0.085 mmol, 1.0 equiv.) in acetonitrile (5 mL) was added TMSI (0.115 mL, 0.85 mmol, 10.0 equiv.) at ° C. After stirring at RT for 10 min, the reaction wag quenched with MeOH. The solvent was removed, and the resulting residue was purified on RP-HPLC using a mixture of acetonitrile and H2O (with 0.1% TFA buffer). The fractions of product was concentrated, dissolved in a mixture of methanol and water (2:1), followed by addition of HCl (4 N in 1,4-dioxane, 2 mL). The mixture was concentrated to give (2S,4R)-2-(3-(2-chloro-3-fluorobenzyl)-1-methylureido)-4-hydroxy-5-(phosphonooxy)pentyl 3-phenylisoxazol-5-ylcarbamate (48 mg, 94%) as a white solid. LRMS (M+H+) m/z 601.5.

Workup

  1. customthe reaction wag quenched with MeOH
  2. customThe solvent was removed
  3. customthe resulting residue was purified on RP-HPLC
  4. additiona mixture of acetonitrile and H2O (with 0.1% TFA buffer)
  5. concentrationThe fractions of product was concentrated
  6. dissolutiondissolved in a mixture of methanol and water (2:1)
  7. additionfollowed by addition of HCl (4 N in 1,4-dioxane, 2 mL)
  8. concentrationThe mixture was concentrated

Sources & evidence

ORD record
ord-909ba502ce624097b6117b375564f3dd
Source dataset
uspto-grants-2014_06
Patent number
US08759374B2

Reaction notes

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